Uroporphyrinogen III decarboxylase

Porphyria cutanea tarda is the most common form. It is inherited as an autosomal dominant trait and is due to deficiency of uroporphyrinogen III decarboxylase. Clinical... 

Figure 2-1 Schematic representation of the heme biosynthetic pathway in mammalian cells. ALAS, S-aminolevulinate synthase PBGS, porphobiUnogen synthase PBGD, porphobilinogen deaminase Uro III synthase, uroporphyrinogen III synthase Uro III decarboxylase, uroporphyrinogen III decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase FC, ferrochelatase.

Scheme 14.29. A representation of a potential pathway for uroporphyrinogen III decarboxylase catalysis to form coproporphyrinogen III (after Martins, B. M. Grimm, B. Mock, H.-F Huber, R. Messerschmidt, A. J. Biol Chem., 2001,276,44108).

Propionibacteria synthesize considerable quantities of compounds with the porphyrin structure, which accumulate both in the cell and in the medium (Muller et al., 1970). Porphyrins are represented mainly by coproporphyrins III, indicating high uroporphyrinogen III decarboxylase activity and relatively low activities of the enzymes catalyzing further steps of the coproporphyrin transformation into heme. Uroporphyrin III and corriphyrins are also found in growing cultures of P. coccoides (Bykhovsky et al., 1987). 

Affected enzyme ALA-dehy- dratase Hydroxymethyl-bilane synthase Uroporphyrinogen III synthase Uroporphyrinogen decarboxylase Coproporphyrinogen oxidase Protoporphyrinogen oxidase Ferrochelatase... 

Figure 3 The synthesis of heme from glycine and sucdnyl-CoA. The enzymes are ALAS, S-aminolevulinic acid (ALA) synthase ALAD, S-aminolevulinic acid dehydratase PBGD, porphobilinogen deaminase UROIIIS, uroporphyrinogen III synthase UROD, uroporphyrinogen decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase and FECH, ferrochelatase.

The genes for all the enzymes of human heme biosynthesis have been characterized (Table 32-2), and the structures of 5-aminolevulinic acid dehydratase (ALAD), hydroxymethyl-bilane synthase (HMBS), uroporphyrinogen-III synthase (UROS), uroporphyrinogen decarboxylase (UROD), and ferrochelatase (FECH) have been determined by x-ray crys-tallography. - - ... 

Luo J, Lim CK. Order of uroporphyrinogen-ill decarboxylations on incubation of porphobilinogen and uroporphyrinogen-III with erythrocyte uroporphyrinogen decarboxylase. Biochem J 1993 289, 519-523. 

Fig. 1. Heme biosynthetic pathway. Steps are catalyzed by 7, -aminolevulinic acid (ALA) synthetase 2, ALA dehydratase 3, uroporphyrinogen I synthetase (PBG deaminase) 4, uroporphyrinogen III cosynthetase 5, uroporphyrinogen decarboxylase 6, coproporphyrinogen oxidase 7, protoporphyrinogen oxidase and 8, ferrochelatase (heme synthetase)...

Uroporphyrinogen decarboxylase 1 Coproporphyrinogen III Porphyria cutanea tarda (AD,1q34) J... 

Uroporphyrinogen decarboxylase catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. The coporphyrinogen III can be oxidized to protoporphyrinogen IX, which is then oxidized to protoporphyrin IX. Ferrochelatase then inserts ferrous iron to form heme. The last three steps take place in the mitochondrion. 

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